Dietary arginine supplementation attenuates renal damage after relief of unilateral ureteral obstruction in rats.

TitleDietary arginine supplementation attenuates renal damage after relief of unilateral ureteral obstruction in rats.
Publication TypeJournal Article
Year of Publication2005
AuthorsIto K, Chen J, Seshan SV, Khodadadian JJ, Gallagher R, Chaar MEl, E Vaughan D, Poppas DP, Felsen D
JournalKidney Int
Volume68
Issue2
Pagination515-28
Date Published2005 Aug
ISSN0085-2538
KeywordsAnimals, Arginine, Cyclic GMP, Dietary Supplements, Enzyme Inhibitors, Fibroblasts, Fibrosis, Glomerular Filtration Rate, In Situ Nick-End Labeling, Kidney, Macrophages, Male, NG-Nitroarginine Methyl Ester, Nitrates, Nitric Oxide, Nitric Oxide Synthase, Nitric Oxide Synthase Type II, Nitric Oxide Synthase Type III, Nitrites, Organ Size, Proliferating Cell Nuclear Antigen, Rats, Rats, Sprague-Dawley, Transforming Growth Factor beta, Transforming Growth Factor beta1, Ureteral Obstruction
Abstract

BACKGROUND: Progression of renal injury after relief of unilateral ureteral obstruction (UUO) has been demonstrated. Nitric oxide (NO) may be an effective intervention due to its vasodilatory, antifibrotic, and anti-apoptotic effects. Herein, we used dietary L-arginine (ARG) supplementation in a UUO relief model.

METHODS: This study comprised group 1, control (no treatment). All other rats were subject to 3-day UUO, which was then relieved, and the rats maintained for 7 additional days. Group 2, no additional treatment; group 3, L-ARG; group 4, L-NAME, NO synthase inhibitor; group 5, ARG and L-NAME. Urinary NO(2/3) was quantified. GFR and ERPF were measured at day 10. Interstitial fibrosis and fibroblast expression, macrophage infiltration, tubular apoptosis, and proliferation, NOS expression, and the levels of tissue TGF-beta were evaluated.

RESULTS: Urinary NO(2/3) was significantly increased by ARG treatment and decreased by L-NAME. GFR and ERPF measured 7 days following relief were not significantly different in the previously obstructed kidneys (POK) of groups 2 and 3. L-NAME significantly reduced GFR and ERPF in the POK. ARG significantly reduced apoptosis, macrophage infiltration, and fibroblast expression in the POK. L-NAME exacerbated the effects on apoptosis and fibroblasts. Fibrosis was minimal in groups 1 through 3, but was significantly increased by L-NAME. ARG did not affect renal NOS expression and tissue TGF-beta1 levels.

CONCLUSION: Dietary ARG supplementation during UUO relief did not improve ERPF or GFR. However, renal damage, including fibrosis, apoptosis, and macrophage infiltration was significantly improved by ARG treatment. This suggests that increasing NO availability could be beneficial in the setting of UUO relief.

DOI10.1111/j.1523-1755.2005.00429.x
Alternate JournalKidney Int
PubMed ID16014028
Grant ListR01-DK58355 / DK / NIDDK NIH HHS / United States
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